TRANSLATIONAL EXAMINATION OF CANNABIS-RELATED CHANGES IN DIURNAL STRESS RHYTHMS

Nicholas C. Glodosky

doi:10.7273/000006471

Cannabis is the most commonly used federally illicit drug in the United States and cannabis users frequently report stress relief as their primary reason for use. The endocannabinoid system is heavily involved in the neuroendocrine stress response, and recent research suggests that diurnal cortisol rhythms may be disrupted in chronic cannabis users. The purpose of Study 1 was to determine whether human cannabis users demonstrate disruptions in diurnal stress rhythms in their natural environments. The purpose of Study 2 was to examine the effects of chronic cannabis vapor self-administration on diurnal corticosterone (CORT) in a rodent model to determine whether cannabis causes these putative dysregulations, or whether pre-existing dysregulations predict cannabis self-administration. For Study 1, 82 human participants (39 cannabis users, 43 non-users) collected saliva samples to quantify cortisol concentrations and gave subjective stress ratings at 8 time points throughout the day and wore a medical-grade sensor device for 24 hours to record physiological indicators of stress (heart rate variability, electrodermal activity). Cannabis users were asked to collect additional samples before and after cannabis use to examine the acute effects of cannabis use. Cannabis users exhibited significant dysregulations in diurnal cortisol rhythms, including a flattened cortisol awakening response and flattened diurnal cortisol slope, as well as elevated cortisol in the afternoon. There were no differences in diurnal heart rate variability or diurnal electrodermal activity between cannabis users and non-users except for elevated heart rate in the evening in cannabis users. Finally, there were significant decreases in cortisol, subjective stress, and features of electrodermal activity following acute cannabis use in cannabis users. For Study 2, 64 Long Evans rats (32 male, 32 female) were randomly assigned to self-administer cannabis or vehicle vapor for 28 days. Prior to self-administration, blood samples were collected to quantify CORT and calculate the diurnal CORT slope at baseline. Following self-administration, blood samples were again collected to examine changes in CORT slopes from baseline. Female rats had elevated CORT both before and after self-administration compared to males, regardless of time or treatment condition. After self-administration, males’ diurnal CORT slopes were steeper compared to baseline and compared to female slopes. However, this effect was not specific to cannabis and was also found in the vehicle control group. The results of these studies provide evidence for the presence of dysregulated diurnal cortisol rhythms in human cannabis users as well as for the acute stress-relieving properties of cannabis in a naturalistic environment. Results from the rodent study provide evidence that vapor alone may be sufficient to induce changes in diurnal CORT. Collectively, these findings indicate that the relationship between cannabis use and diurnal cortisol rhythms is complex and associations between cannabis use and flattened diurnal cortisol slopes may be driven by outside variables unique to humans (e.g. burnout, fatigue, Post Traumatic Stress Disorder).

TRANSLATIONAL EXAMINATION OF CANNABIS-RELATED CHANGES IN DIURNAL STRESS RHYTHMS

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